The neuropeptides, vasopressin and oxytocin, are present in brain stem regions important in cardiovascular regulation. Results show that the spontaneously hypertensive rat (SHR) exhibits a specific deficit in these neuropeptides; with the changes occurring in the paraventricular nucleus and brain stem. Thus, brain peptides, in particular the neurohypophyseal hormones, may be important in the control of cardiovascular homeostasis and possibly in the etiology of hypertension. We propose to investigate the mechanisms controlling both blood pressure, and vasopressin and oxytocin synthesis. A protocol for the study of biosynthesis has been established; it involves the incorporation of a labeled amino acid, purification by molecular weight and high performance liquid chromatography (HPLC) and identification by immunochemical techniques. The synthesis of the high molecular weight precursors, neurophysins and the peptides will be determined in specific brain regions, namely, the magnocellular nuclei, median eminence, posterior pituitary and brain stem. The goals of the project are: 1) To investigate hypothalamic and neurohypophyseal peptide biosynthesis in genetic hypertension (SHR). This is designed to evaluate the changes in peptidergic activity associated with the development of the high blood pressure, and 2) To assess the possible relationship between the high blood pressure and the changes in central peptidergic activity. The SHRs will be treated with the antihypertensive drug, propranolol, and the effects on blood pressure and neurohypophyseal peptides determined. This research proposal is based on the hypothesis that the central neuropeptides, vasopressin and oxytocin, may act as neurotransmitters or neuromodulators, and may be important in the control of blood pressure. Furthermore, derangements in this axis may be critical in the development of the increased blood pressure of the SHR. The results from these experiments should answer basic questions on the role of hypothalamic neuropeptides in the regulation of cardiovascular function.